Biomedical subjects

K Weber

Publications and source records attributed to K Weber.

At least 163 records · Page 9Linked to original sources

PubMed1997

Effects of tennis training on lipid metabolism and lipoproteins in recreational players.

OBJECTIVE: To investigate the short term effects of tennis training on lipid metabolism and to find out if a typical tennis training programme has positive longitudinal effects on cardiovascular risk factors in recreational players. METHODS: The experimental design consisted of an exercise study and a subsequent longitudinal study. In the exercise study the short term metabolic effects of a two hour technically orientated tennis training (TT) session and a running intensive tennis training (RIT) session were investigated in 16 recreational tennis players (eight men: 46 (SD 7) years, 177 (6) cm, 81 (10) kg; and eight women: 44 (5) years, 165 (5) cm, 64 (6) kg). In the longitudinal study the long term effects of a six week RIT programme in 22 players (11 men and 11 women) of similar characteristics were compared with those in 16 control subjects (eight men and eight women). The results of the exercise study (higher lipolytic activity and cardiopulmonary demand, as well as acceptance by the players) led to the RIT method being chosen for all training sessions in the longitudinal study. RESULTS: In RIT, significantly higher values for heart rate (148 (SD 10) v 124 (11) beats/minute) and lactate (2.8 (1.1) v 1.5 (0.6) mmol/l), significantly higher post exercise concentrations of serum glycerol (0.37 (0.15) v 0.29 (0.14) mmol/l) and high density lipoprotein cholesterol (1.31 (0.55) v 1.20 (0.50) mmol/l) and a higher acceptance than in TT (15 of the 16 players preferred RIT) were found. During the six week tennis training programme the changes in body weight (-1.41 (1.56) v 0.00 (1.50) kg) and anaerobic threshold (1.04 (0.84) v -0.08 (0.92) km/h) were significantly different between the training and control group. In the training group several parameters of the lipoprotein profile tended to change in an antiatherosclerotic direction. CONCLUSIONS: The results indicate that typical regular tennis training influences cardiovascular risk factors in a positive manner and can be suggested as an attractive alternative to other current health orientated sports programmes. A more frequent use of running intensive exercises during tennis training is recommended.

Adult↗

PubMed1997

Effect of exercise intensity on free tryptophan to branched-chain amino acids ratio and plasma prolactin during endurance exercise.

The potential of exercise-induced changes in peripheral amino acids to alter blood prolactin levels through a serotonergic system modification was investigated in 8 male athletes. In two trials, subjects (N = 8) exercised on a cycle ergometer for 5 hr. The intensity of exercise corresponded to 55% VO2max (T55) or 75% VO2max (T75), respectively. In each trial, each subject received a 25-g energy bar (111 kcal) every 60 min, as well as 300 ml of a 6% carbohydrate solution (90 kcal) every 30 min of exercise duration. Plasma glucose and insulin declined (p < or = .05) in both trials during exercise. Ammonia was augmented (p < or = .05) above the baseline concentration after 120 min in both trials. During the last 2 hr of exercise, plasma free fatty acids were higher (p < or = .05) in T75 than in T55. During this time, the plasma free TRP/BCAA ratio was also augmented (p < or = .05) in T75, while no change was induced in T55. Plasma prolactin did not change in T55, while an increase (p < or = .05) was found in T75. The findings may further support the hypothesis that during endurance exercise changes in peripheral amino acid concentration may influence prolactin response via serotonergic system modifications.

Adult↗

PubMed1997

Identification and characterization of a novel type of annexin-membrane interaction: Ca2+ is not required for the association of annexin II with early endosomes.

Annexin II, a member of a family of Ca2+ and membrane binding proteins, has been implicated in regulating membrane organization and membrane transport during endocytosis and Ca2+ regulated secretion. To characterize the mechanistic aspects of the annexin. II action we studied parameters which determine the endosomal association of annexin II. Immunoblot analysis of subcellular membrane fractions prepared from BHK cells in the presence of a Ca2+ chelating agent reveals that annexin II remains associated with endosomal membranes under such conditions. This annexin II behaviour is atypical for the Ca2+ regulated annexins and is corroborated by the finding that ectopically expressed annexin II mutants with inactivated Ca2+ binding sites continue to co-fractionate with endosomal membranes. The Ca(2+)-independent membrane association of annexin II is also not affected by introducing mutations interfering with the complex formation of annexin II with its intracellular protein ligand p11. However, a deletion of the unique N-terminal domain of annexin II, in particular the sequence spanning residues 15 to 24, abolishes the Ca(2+)-independent association of the protein with endosomes. These results describe a novel, Ca(2+)-independent type of annexin-membrane interaction and provide a first explanation for the observed preference of different annexins for different cellular membranes. In the case of annexin II this specificity could be mediated through specific membrane receptors interacting with a unique sequence in the annexin II molecule.

Amino Acid Sequence↗

PubMed1997

Subpellicular and flagellar microtubules of Trypanosoma brucei are extensively glutamylated.

To determine the spectrum of tubulin variants in cytoskeletons of Trypanosoma brucei carboxy-terminal fragments of alpha- and beta-tubulin were isolated and characterized by sequencing and mass spectrometry. All variants arise by posttranslational modifications. We confirm the presence of tyrosinated and detyrosinated alpha-tubulin. Unexpectedly, but in line with its sequence, beta-tubulin also occurs with and without its carboxy-terminal tyrosine. Both tyrosinated and detyrosinated alpha- and beta-tubulins are extensively glutamylated. Unglutamylated tubulins are only trace components of the cytoskeletal microtubules. The maximal numbers of glutamyl residues in the lateral chain are 15 and 6 for alpha- and beta-tubulin, respectively. The oligoglutamyl side chain is linked via an isopeptide bond to glutamic acid residues 445 of alpha- and 435 of beta-tubulin. The same sites are used in glutamylated tubulins of mammalian brain. No tubulin variants based on polyglycylation are detected in cytoskeletal preparations or in isolated flagella. Tubulin specific incorporation of radioactive glutamate but not of glycine is observed when protein biosynthesis is completely inhibited in Trypanosoma cells. Possible reasons for the absence of polyglycylated tubulins from the trypanosomal axoneme are discussed. Finally we show that lysine 40 of the flagellar alpha-tubulin is completely acetylated.

Amino Acid Sequence↗

PubMed1997

Bone density variation and its effects on risk of vertebral deformity in men and women studied in thirteen European centers: the EVOS Study.

In Europe there is a 3-fold variation, according to geographical center, in risk of vertebral deformity in men and women over the age of 50. We investigated the relationship between bone density, as assessed by dual-energy X-ray absorptiometry (DEXA) of the spine and hip and prevalent vertebral deformities in 13 of the 36 centers participating in the European Vertebral Osteoporosis Study (EVOS). Each center recruited an age-stratified sample of men and women aged 50 years and over, and of those who agreed to densitometry, 288/2088 women and 233/1908 men were found to have one or more deformities of the vertebrae between T4 and L4 as assessed by the McCloskey algorithm. DEXA was in each case performed on L2-L4, the proximal femur, or both. Bone densitometry results were cross-calibrated between centers using the European Spine Phantom prototype and results expressed as bone mineral density (BMD, g/cm2). In both genders, subjects with deformities involving loss of anterior vertebral body height alone comprised over 20% of the total with deformities and these related poorly to BMD. Other classes of deformity were found by logistic regression to relate significantly to BMD in one or both genders, with odds ratios for the risk of any of these ranging from 1.67 to 2.11 for a 1 SD reduction in bone density at spine, femoral neck, or trochanter (p < 0.001). Adjusting for anthropometric variables and BMD did not remove the effect of age on risk which rose 1.67- to 1.78-fold per decade according to gender. The greater unadjusted rate of increase in deformity risk with age in women was attributable to their faster rate of bone loss with age; after adjusting for age, body mass index (BMI), and BMD at the trochanter in grams per square centimeter, men had a 2-fold higher risk of deformity than women. Analysis of the relationship between mean bone density and the prevalence of deformity in each center demonstrated no significant differences between centers in either gender, after adjusting for BMD, age, and BMI together with an a posteriori statistical adjustment for imperfect cross-calibration of densitometers. It is concluded that BMD is an important determinant of deformity risk in both genders. Together with age, BMD explains much of the differences in risk both between the sexes and between individual geographical centers in Europe.

Aged↗

PubMed1997

A new mtDNA mutation showing accumulation with time and restriction to skeletal muscle.

We have identified a new mutation in mtDNA, involving tRNALeu(CUN) in a patient manifesting an isolated skeletal myopathy. This heteroplasmic A-->G transition at position 12320 affects the T psi C loop at a conserved site and was not found in 120 controls. Analysis of cultured fibroblasts, white blood cells/platelets, and skeletal muscle showed that only skeletal muscle contained the mutation and that only this tissue demonstrated a biochemical defect of respiratory-chain activity. In a series of four muscle-biopsy specimens taken over a 12-year period, there was a gradual increase, from 70% to 90%, in the overall level of mutation, as well as a marked clinical deterioration. Single-fiber PCR confirmed that the proportion of mutant mtDNA was highest in cytochrome c oxidase-negative fibers. This study, which reports a mutation involving tRNALeu(CUN), demonstrates clearly that mtDNA point mutations can accumulate over time and may be restricted in their tissue distribution. Furthermore, clinical deterioration seemed to follow the increase in the level of mutation, although, interestingly, the appearance of fibers deficient in respiratory-chain activity showed a lag period.

Base Sequence↗

PubMed1997

Specific genetic changes of diagnostic importance in chromophobe renal cell carcinomas.

The histologic diagnosis of chromophobe renal cell carcinomas is often uncertain because of phenotype overlap among different types of kidney cancers. Recently, in a novel genetic classification of renal cell tumors, a combination of monosomies of chromosomes 1, 2, 3, 6, 10, 13, 17, and 21 have been suggested to have a diagnostic value for this unique type of tumor. Therefore, we have analyzed fresh and paraffin-embedded tissues obtained from 42 chromophobe renal cell carcinomas for allelic losses at the above-mentioned chromosomal regions by employing microsatellite markers. Loss of chromosomes 1, 2, 6, 10, 13, and 17 was detected in between 75% and 95% of tumors, and loss of chromosome 21 was observed in 54% of cases. All but one tumor showed a combination of monosomies at the specific chromosomes. Thus, applying the set of microsatellite markers used in this study, a PCR-based diagnosis of chromophobe renal cell carcinomas could be established within 1 to 2 days. The general applicability of this approach to fresh and paraffin-embedded tissues allows a correct genetic characterization in all cases where a diagnosis based on histopathology remains uncertain.

Alleles↗

PubMed1997

Metabolic and ergogenic effects of carbohydrate and caffeine beverages in tennis.

OBJECTIVE: Metabolic and ergogenic effects of carbohydrate and caffeine concentrations, common in commercial available beverages, were investigated in 16 tournament players (8 males and 8 females) during a 4 hrs interrupted tennis match (30 min rest after 150 min). METHODS: On three double-blind occasions players ingested a placebo (PLA), carbohydrate (CHO) or caffeine drink (CAF) at court changeover and during the resting period. In men (women) total intake consisted of 2.8 l (2.0 l) fluid, supplemented with 243 g (182 g) carbohydrates (CHO) or with 364 mg (260 mg) caffeine (CAF), respectively. Postexercise all players performed a ball-machine test (BMT) and a tennis-sprint test (TST). RESULTS: During match play blood glucose (GLU) was higher in CHO and did not differ between CAF and PLA. Immediately after the resting period GLU temporary declined in CHO and PLA, while no significant changes occurred in CAF. Increases of serum FFA and glycerol as well as the decrease of insulin were similar during the PLA and CAF trials and less pronounced in CHO. Postexercise urine concentrations of epinephrine and caffeine were significantly higher in CAF. Perception ratings and hitting accuracy (BMT) were not affected by treatment. CHO resulted in higher blood lactate levels during match play and a better post-exercise sprint performance (TST). Under CAF women won significantly more games than during both other treatments. CONCLUSIONS: CHO enhances tennis-specific running-speed but has no ergogenic effect on tennis performance under the conditions of our study. CAF improves glucose homeostasis at the beginning of work load after rest and may increase tennis success in women.

Adrenergic Agonists↗

PubMed1996

Annexin II modulates volume-activated chloride currents in vascular endothelial cells.

The membrane-associated, microfilament-binding protein annexin II is abundantly expressed in endothelial cells from calf pulmonary artery (CPAE cells). We have analyzed its role in the regulation of volume-activated chloride currents (ICl, vol) by loading the cells via the patch pipette with a peptide comprising the N-terminal 14 residues of annexin II. This sequence harbors the binding site for the intracellular annexin II ligand, p11, and the peptide interferes with the annexin II-p11 complex formation. Loading of a CPAE cell with this peptide caused a gradual decrease in the amplitude of ICl, vol during repetitive stimulations with a 28% hypotonic extracellular solution. This run down of the current was virtually absent in untreated cells and in cells that were loaded with a mutated 14-amino acid peptide, which has a single amino acid replacement known to result in a more than 1000 times reduced affinity for binding to p11. We conclude that annexin II-p11 complex formation is either directly or indirectly involved in the activation of ICl, vol in endothelial cells.

Animals↗

PubMed1996

Nucleotide sequence of two actin genes of Lumbricus terrestris.

Two actin genes (act1-LUM and act2-LUM) of the annelid Lumbricus terrestris are characterised. Both genes reveal a single intron of 632 or 696 bp, respectively, located at exactly the same position. This intron position is currently the only intron position shared by some protostomic and most deuterostomic actin genes.

Actins↗

PubMed1996

Structural requirements for annexin I-S100C complex-formation.

S100C is a member of the S100 family of EF-hand-type Ca(2+)-binding proteins which are thought to bind to and thereby regulate the activity of cellular target proteins in a Ca(2+)-dependent manner. An intracellular ligand for S100C is the Ca2+/phospholipid-binding protein annexin I and we show here that complex-formation is mediated through unique domains within S100C and annexin I. Using a proteolytically truncated annexin I derivative as well as a number of N-terminal annexin I peptides in liposome co-pelleting and ligand-blotting assays we map the S100C-binding site to the N-terminal 13 residues of annexin I. Similar analyses employing recombinantly expressed S100C mutants reveal that residues D91 to 194 in the unique C-terminal extension of this S100 protein are indispensable for annexin I binding. Interaction between S100C and an N-terminal annexin I peptide containing a tryptoplan at position 11 can also be monitored by fluorescence emission spectroscopy after tryptophan excitation. This analysis indicates that the local environment of the tryptophan in annexin I becomes less aqueous on S100C binding, suggesting a hydrophobic nature of the protein-protein interaction. Thus the structural basis of the annexin 1-S100C complex-formation probably resembles to a large extent that of the well-characterized annexin II-p11 interaction.

Animals↗

PubMed1996

Regulation of cADP-ribose-induced Ca2+ release by Mg2+ and inorganic phosphate.

cADP-ribose (cADPr) has recently been shown to release Ca2+ from an intracellular store of permeabilized T lymphocyte cell lines (Guse, A. H., da Silva, C. P., Emmrich, F., Ashamu, G. A., Potter, B. V. L., and Mayr, G. W. (1995) J. Immunol. 155, 3353-3359). Using permeabilized Jurkat and HPB. ALL T lymphocytes, the effects of varying concentrations of inorganic phosphate and Mg2+ on cADPr-induced Ca2+ release were investigated. cADPr-induced Ca2+ release was dependent on the concentration of inorganic phosphate, showing very low Ca2+ release activity between 0.5 and 2 mM inorganic phosphate. At 4 to 5 mM inorganic phosphate, the cADPr-induced Ca2+ release was much more pronounced, reaching maximal values at 10 mM inorganic phosphate. The underlying mechanism for this stimulatory effect was an increased loading of the cADPr-sensitive Ca2+ store, which was demonstrated by enhanced resequestration of Ca2+ selectively into the cADPr-sensitive Ca2+ store. The free Mg2+ concentration also influenced cADPr-induced Ca2+ release in permeabilized cells: at 0 and 8.58 mM the release was nearly completely abolished, whereas at 1.06 mM maximal Ca2+ release by cADPr was observed. High performance liquid chromatographic analysis of exogenously added cADPr revealed that the catabolism of cADPr at varying Mg2+ and Pi concentrations had only minor relevance for the modulatory effects observed. To correlate the effects of inorganic phosphate and Mg2+ on cADPr-induced Ca2+ release observed in the permeabilized cell preparations, measurements of these ions in intact Jurkat T lymphocytes were carried out. Intact Jurkat T cells stimulated via the T cell receptor middle dotCD3 complex did not respond with significant elevation of the free intracellular Mg2+ concentration. In contrast, stimulation via the T cell receptor middle dotCD3 complex resulted in an increase in the intracellular inorganic phosphate concentration. These data indicate a role for the intracellular inorganic phosphate concentration in the regulation of cADPr-mediated Ca2+ release in T lymphocytes.

Adenosine Diphosphate Ribose↗

PubMed1996

Polyglycylation of tubulin in the diplomonad Giardia lamblia, one of the oldest eukaryotes.

We have searched for post-translational modifications in tubulin of the diplomonad Giardia lamblia, which is a representative of the earliest branches in eukaryotic evolution. The carboxyterminal peptide of alpha-tubulin was isolated and characterized by automated sequencing and mass spectrometry. Some 60% of the peptide is unmodified, while the remainder shows various degrees of polyglycylation. The number of glycyl residues in the lateral side chain ranges from 2 to 23. All peptide species encountered end with alanine-tyrosine, indicating the absence of a detyrosination/tyrosination cycle. We conclude that tubulin-specific polyglycylation could be as old as tubulin and axonemal structures.

Amino Acid Sequence↗

PubMed1996

The A and B tubules of the outer doublets of sea urchin sperm axonemes are composed of different tubulin variants.

The alpha beta-tubulin heterodimer, the structural unit of microtubules, comes in many variants. There are different alpha and beta isotypes encoded by multigene families. Additional heterogeneity is generated by a set of posttranslational modifications. Detyrosination of alpha-tubulin, removal of the carboxy-terminal Glu-Tyr dipeptide of alpha-tubulin, phosphorylation of some tubulins, polyglutamylation, and polyglycylation of alpha- and beta-tubulins all involve the acidic carboxy-terminal region. We have investigated the distribution of tubulin variants in the axonemal microtubules of sea urchin sperm flagella by immunological procedures and by direct sequence and mass spectrometric analysis of the carboxy-terminal peptides. The A and B tubules that comprise the nine outer doublets differ strongly in tubulin variants. A tubules contain over 95% unmodified, tyrosinated alpha beta-tubulin. In B tubules, alpha-tubulin is approximately 65% detyrosinated and both alpha- and beta-tubulin are 40-45% polyglycylated. These results show a segregation of tubulin variants between two different axonemal structures and raise the possibility that posttranslational modifications of tubulins reflect or specify structurally and functionally distinct microtubules.

Amino Acid Sequence↗

PubMed1996

NuMA: a bipartite nuclear location signal and other functional properties of the tail domain.

Nuclear Mitotic Apparatus protein (NuMA) is a 238-kDa protein of the nuclear matrix in interphase that relocates to the spindle poles in mitosis. The globular tail domain (residues 1701 to 2115) contains the nuclear targeting sequence, the site for binding to the mitotic spindle as well as a site responsible for nuclear reformation. To more precisely map these sites, we inserted full-length human NuMA and 16 derivatives with increasing truncations of the tail domain into the pCMV5 vector and induced transient expression. NuMA was found in the interphase nucleus of all transfected BHK cells expressing either full-length NuMA or NuMA mutant proteins ending at or after residue 2005. In contrast, mutants ending at or before residue 2003 remained in the cytoplasm. In the full-length NuMA molecule, point mutations at position 1988 or 1989 or a double mutation at residues 2004 and 2005 cause NuMA to accumulate in the cytoplasm of both BHK and HeLa cells. The combined results indicate a bipartite nuclear location signal involving the sequences RKR (1987-1989) and KK (2004-2005) which are separated by 14 amino acid residues. In 30% of BHK cells transfected by the full-length clone, cytoplasmic aggregates of NuMA that colocalize with the centrosomes were documented in addition to the nuclear staining. In cells with large aggregates the cytoplasmic microtubular profile was disturbed. Observation of micronuclei formation suggests that a region important for normal nuclear reformation lies in the C-terminal 130 residues. Finally, NuMA mutant proteins ending at or after residue 1800 bound to the spindle poles of mitotic cells, while NuMA proteins ending at or before residue 1750 did not.

Amino Acid Sequence↗

PubMed1996

Increased adhesiveness of isolated monocytes to endothelium is prevented by vitamin C intake in smokers.

BACKGROUND: To explore pathophysiological mechanisms of cigarette smoking involved in atherogenesis, we compared adhesiveness of isolated blood monocytes with endothelium and plasma levels of the aqueous phase antioxidant vitamin C in nonsmokers and smokers before and after supplementation, using a novel monocyte adhesion assay with fixed human endothelial cells. METHODS AND RESULTS: Monocyte adhesion to unstimulated human umbilical vein endothelial cells ranged from 0.17% to 0.51% in the nonsmoker group (0.37+/-0.09%, mean +/-SD, n=13). In smokers with a 1 to 2 packs per day consumption, monocyte adhesion was increased to 0.71+/-0.17% (mean +/-SD, n=10, P<.001), ranging from 0.46% to 0.99%. Increased adhesiveness was mediated by the integrin CD11b/CD18, as shown by inhibition with a monoclonal antibody to CD11b but not associated with altered CD11b surface expression. Plasma vitamin C levels were reduced in smokers (48.2+/-14.1 micromol/L) versus nonsmokers (67.7+/-17.6 micromol/L; P<.025), while no significant differences were found in retinol, vitamin E, or beta-carotene levels. This confirms that the radical scavenger vitamin C reacts sensitively to oxidative stress induced by cigarette smoke in human plasma. Consistently, dietary supplementation with vitamin C (2 g per day) for 10 days raised plasma levels to 82.6+/-11.0 micromol/L (n=10, P<.001) in smokers and decreased monocyte adhesion to values found in nonsmokers (0.38+/-0.18%, P<.001). In contrast, vitamin C intake did not affect monocyte adhesiveness in nonsmokers (0.37+/-0.14%, n=6) despite increasing plasma levels to 82.9+/-11.8 micromol/L. CONCLUSIONS: Our data show that cigarette smoking increases CD11b-dependent monocyte adhesiveness in humans. Restoring reduced plasma vitamin C concentrations in smokers by oral supplementation decreased monocyte adhesion to values found in nonsmokers.

Adult↗

PubMed1996

The crystal structure and ion channel activity of human annexin II, a peripheral membrane protein.

Annexin II binds in a calcium-dependent manner to acidic phospholipids and is a substrate of some protein kinases. An N-terminally shortened form of human annexin II was crystallized and its molecular structure determined. It is very similar to two previously described members of this protein family, annexin I and annexin V. The protein structure is nearly completely alpha-helical organized as four compact domains which consist of five alpha-helices each. The domains surround a hydrophilic pore. The calcium binding sites are located at the convex side of the structure as in annexin V. Recombinant and natural porcine annexin II are active as ion channel with characteristics similar to annexin V, while N-terminally shortened annexin II and the heterotetramer (annexin II-p11)2 are inactive. Two cysteine residues, Cys133 and Cys262, form a disulphide bridge connecting domains II and III, adding further weight to the notion that ion channel activity does not require major structural rearrangements.

Amino Acid Sequence↗

PubMed1996

Specific recognition of coiled coils by infrared spectroscopy: analysis of the three structural domains of type III intermediate filament proteins.

The central domain of cytoplasmic intermediate filament (IF) proteins from vertebrates contains some 310 residues and forms a double-stranded coiled coil (rod) with a length of about 46 nm. The flanking terminal domains show a high cell type specific variability both in sequence and in length. Using Fourier transform infrared (FTIR) spectroscopy we measured secondary structures of isolated domains of type III and IV IF proteins and of the soluble tetramers and the filaments formed by type III IF proteins. The amide I spectrum of the desmin rod is virtually identical to the spectra of other coiled-coil proteins such as tropomyosin and the myosin rod. All these double-stranded coiled coils reveal spectra distinctly different from classical alpha-helical spectra. The spectrum of coiled coils is a triplet of approximately equally strong bands. One band occurs at normal alpha-helix position, while the other two are found at lower wavenumbers. Theoretical aspects of these findings are discussed in the accompanying paper by W. C. Reisdorf and S. Krimm [(1996) Biochemistry 35, 1383-1386]. The amino-terminal head domain of desmin has a multicomponent spectrum with major fractions of beta-sheet. The carboxy-terminal tail domains of desmin and the neurofilament proteins L and H, the latter in the phosphorylated and in the dephosphorylated forms, have very similar FTIR spectra, indicating mostly random structure. The spectrum of desmin type III protofilaments is very similar to the sum of the spectra of the three isolated domains. Polymerization into filaments seems to induce a small change in secondary structure.

Desmin↗